Impact of ursodeoxycholic acid on histologic and immunophenotypic features in primary biliary cholangitis

Primary biliary cholangitis (PBC) is an immune-mediated cholangiopathy for which ursodeoxycholic acid (UDCA) improves biochemical outcomes and survival, but its effects on tissue phenotype remain uncertain. We examined whether morphology and marker expression change with UDCA status or primarily reflect disease severity.

We studied 109 specimens (biopsies and explants) from 67 patients with PBC: 9 same-episode PRE-POST pairs for the primary paired analysis and all 109 specimens for secondary cross-sectional analysis. Semiquantitative scores were analyzed using exact Wilcoxon signed-rank tests and proportional-odds ordinal regression with patient-clustered robust standard errors and Benjamini-Hochberg correction.

Among 9 paired patients, no feature differed PRE-POST (all q = 1.00), including CK7 (P = .125), CK19 (P = .25), and fibrosis (P = .656). However, 80%-power minimum detectable differences were 0.89 (S100) and 1.19 (CD1a) units on a 0-3 scale, limiting inference. In fibrosis-adjusted cross-sectional models, UDCA status was not associated with any marker (all q ≥ .95), whereas fibrosis was associated with CK7 (OR 1.37, 95% CI 1.11-1.69; q = .007), CK19 (OR 1.79, 1.45-2.22; q < .001), and CD1a⁺ density (OR 1.31, 1.09-1.57; q = .007); CP grade was exploratory (OR 1.21; q = .021). After explant adjustment, CK7 and CK19 associations persisted, whereas CD1a⁺ and CP grade did not; S100⁺ was not significant in either model.

Fibrosis stage, not UDCA status, was the principal correlate of biliary epithelial marker expression. No within-patient change was detected, although changes below one-third of the scoring scale could not be excluded. CK7 and CK19 primarily reflect disease stage rather than treatment effect.